We
herein
report
a
photoredox
N–S
coupling
reaction
between
dialkyl
azodicarboxylates
and
thiols
to
access
sulfenamide
scaffolds.
This
proceeds
under
mild,
green,
operationally
simple
conditions,
offering
broad
scope
of
sulfenamides
with
high
yields
excellent
atom
efficiency.
Mechanistic
investigations
revealed
this
followed
photoinitiated
radical
pathway
in
which
iodide
plays
crucial
role
as
both
initiator
single-electron
reductant.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
While
sulfoximines
are
nowadays
a
well
established
functional
group
for
medicinal
chemistry,
the
properties
of
sulfilimines
significantly
less
studied,
and
no
sulfilimine
has
progressed
to
clinic
date.
In
this
account,
physicochemical
in
vitro
reported
compared
those
other
more
traditional
groups.
Furthermore,
impact
on
real
drug
scaffolds
is
studied
two
series
sulfilimine-containing
analogs
imatinib
hNE
inhibitors.
We
show
that
can
be
chemically
configurationally
stable
under
physiologically
relevant
conditions
they
basic
highly
polar
thus
often
beneficial
solubility
metabolic
stability,
although
at
cost
reduced
permeability.
conclude
S-cyclopropyl,S-(hetero)aryl
S,S-di(hetero)aryl
so
far
neglected
but
potentially
valuable
S(IV)
based
pharmacophores
deserve
considered
as
part
chemistry
toolbox.
A
copper-catalyzed
Ullmann-type
cross-coupling
reaction
of
sulfenamides
with
aryl
iodides
is
developed.
The
key
to
success
the
use
a
2-methylnaphthalen-1-amine-derived
amide
ligand,
which
enables
formation
an
S-C
bond
access
functionalized
sulfilimines
in
good
excellent
yields
at
room
temperature.
This
method
has
advantages
mild
conditions,
broad
substrate
scope,
functional
group
compatibility,
and
high
chemoselectivity.
utility
this
protocol
highlighted
through
late-stage
modification
drug-relevant
molecules
sulfilimine
product
derivatization.
Abstract
Sulfur-containing
compounds
are
found
in
myriad
applications.
Sulfones
and
sulfonamides
the
most
common
functional
groups
used
medicinal
agrochemical
endeavours.
Isosteres
of
these
groups,
for
example,
sulfoximines
sulfonimidamides,
emerging
functionalities,
they
increasingly
relevant
patent
literature.
However,
general,
associated
synthetic
routes
still
have
limitations,
including
use
harsh
reaction
conditions
highly
reactive
reagents.
A
variety
catalytic
reactions
that
employ
a
diverse
range
substrate
classes
been
developed
to
address
issues.
This
short
review
highlights
recent
syntheses
aza-sulfur
compounds,
which
we
hope
will
open
new
directions
discovery
chemistry.
1
Introduction
2
Reactions
N-Sulfinylamines
3
with
Sulfenamides
4
Sulfinates
5
Sulfinamides
6
Other
Aza-Sulfur
Compounds
7
Conclusion
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 28, 2025
Sulfoximines
are
increasingly
utilized
in
pharmaceuticals
and
agrochemicals
with
all
sulfoximine
clinical
candidates
incorporating
either
an
S-methyl
or
S-cyclopropyl
substituent.
Here,
we
report
on
a
general
efficient
sequence
for
the
asymmetric
synthesis
of
both
these
substitution
patterns.
The
sulfilimine
intermediates
by
first
Ru-catalyzed
enantioselective
alkylation
sulfenamides
enables
examples
S-alkylation
monosubstituted
diazo
compounds.
reaction
proceeds
at
≤1
mol
%
Ru-catalyst
loading,
tert-butyl
diazoacetate,
high
yields
≥98:2
er
achieved
exceedingly
broad
range
sulfenamides,
including
S-(hetero)aryl,
-alkenyl,
-methyl,
-benzyl,
-branched
alkyl,
-tert-butyl
substituents
sterically
electronically
diverse
N-acyl
groups.
Sulfenamides
derived
from
densely
functionalized
advanced
drug
also
alkylated
99:1
er.
After
oxidation
N-pivaloyl
S-tert-butyl
acetate
substituted
to
corresponding
sulfoximine,
treatment
trifluoracetic
acid
aprotic
solvent
resulted
decarboxylation
while
aqueous
HCl
cleavage
group
give
NH
sulfoximine.
Alternatively,
dibromoethane
followed
acid-mediated
provided
preclinical
candidate
LTGO-33
formal
phase
II
ART0380
demonstrate
utility
disclosed
approach.
The Journal of Organic Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 18, 2024
An
iron-catalyzed
nitrene
transfer
reaction
for
the
rapid
synthesis
of
sulfinamidines
from
readily
available
sulfenamides
is
reported.
This
method
features
mild
conditions,
short
times,
and
a
broad
substrate
scope,
allowing
preparation
variety
in
good
to
excellent
yields.
The
synthetic
utility
sulfinamidine
products
was
further
demonstrated
through
their
conversion
other
valuable
sulfur(VI)
compounds,
such
as
sulfondiimidoyl
fluorides,
sulfinamidiate
esters,
sulfonimidamides.
Preliminary
efforts
development
an
asymmetric
variant
showed
moderate
enantioselectivity.
The Journal of Organic Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 16, 2024
In
this
study,
a
metal-free
and
efficient
method
for
the
synthesis
of
sulfilimines
o-sulfanylanilines
in
high
yields
with
excellent
chemoselectivities
from
oxonium
aryne
precursors
sulfenamides
has
been
developed.
This
features
mild
reaction
conditions,
simple
operations,
general
substrate
scope,
good
tolerance
functional
groups.
addition,
scale-up
synthesis,
related
applications,
preliminary
mechanistic
explorations
were
also
investigated.
Angewandte Chemie,
Год журнала:
2024,
Номер
136(35)
Опубликована: Май 15, 2024
Abstract
Sulfinamidines
are
promising
aza‐S
IV
chiral
building
blocks
in
asymmetric
synthesis
and
drug
discovery.
However,
no
report
has
documented
their
enantioselective
synthesis.
Here
we
present
an
of
sulfinamidines
via
electrophilic
amination
sulfenamides
using
enantiopure
N−H
oxaziridine.
The
resulting
enantiomerically
enriched
primary
configurationally
stable
at
90
°C
solution
show
remarkable
stability
against
organic
acids
bases
under
non‐aqueous
conditions.
We
also
demonstrate
a
one‐pot,
three‐component,
sulfinamides
oxaziridine
reagents.
